Directed Evolution of Enantioselective Enzymes: An Unconventional Approach to Asymmetric Catalysis in Organic Chemistry

Abstract

In the mid-1990s, I initiated in my group an unusual kind of project which is perhaps strange for a synthetic organic chemist who was otherwise focusing on the development of chemo-, regio-, and stereoselective organometallic reagents and catalysts. The basic idea was to imitate evolution in Nature in the quest to create enantioselective enzymes for application in synthetic organic chemistry. Rather than relying on design based on the assessment of steric and electronic effects (and on experience and serendipity), which was and still is the usual procedure in research regarding stereoselective transition-metal-based catalysis, the underlying idea was to harness in the laboratory the powerful driving force inherent in Darwinian principles comprising iterative cycles of mutation and selection. In this Perspective, composed on the occasion of the 2009 Arthur C. Cope Award address, I focus on the principles, successes, and future challenges of this unconventional approach to asymmetric catalysis.